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Stem definition	Drug id	CAS RN
Hepatitis Virus C (HVC) protease inhibitors	4812	923604-59-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: olysio TMC-435 TMC435350 simeprevir simeprevir sodium	Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS. Molecular weight: 749.94 Formula: C38H47N5O7S2 CLOGP: 5.45 LIPINSKI: 3 HAC: 12 HDO: 2 TPSA: 156.89 ALOGS: -5.39 ROTB: 7 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

olysio
TMC-435
TMC435350
simeprevir
simeprevir sodium

Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.

Molecular weight: 749.94
Formula: C38H47N5O7S2
CLOGP: 5.45
LIPINSKI: 3
HAC: 12
HDO: 2
TPSA: 156.89
ALOGS: -5.39
ROTB: 7

Status: OFM

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
S (Water solubility)	0.00 mg/mL	Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	4.218		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	23.442		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	5	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	4.656	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	0.240	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	0.480	%	High	1
herg	hERG pIC50	4.752	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	4.457	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	25.351	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	0.290	%	High	1
kinase-safety-class	ACVR2B,EIF2AK3,GRK2,MAPK10,PDK1,PDK2,PDK4,PRKDC	8
kinase-selectivity-class	PDK1	1
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	12.417		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	6.471		High	1
mppb	Mouse plasma protein binding (% unbound)	0.210		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	104.713		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	0.420	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	9.750	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	1.460	%	High	1
rppb	Rat plasma protein binding (% unbound)	0.250	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	21.827	uM	High	1

Approvals:

Date	Agency	Company	Orphan
May 14, 2014	EMA
Nov. 22, 2013	FDA	JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	841.74	40.48	301	4422	136668	90487056
Anaemia	640.02	40.48	326	4397	352476	90271248
White blood cell count decreased	507.24	40.48	221	4502	166888	90456836
Blood bilirubin increased	416.85	40.48	134	4589	43336	90580388
Neutrophil count decreased	291.32	40.48	117	4606	71415	90552309
Haemoglobin decreased	255.03	40.48	137	4586	161819	90461905
Hyperbilirubinaemia	175.39	40.48	53	4670	13883	90609841
Haemolytic anaemia	162.43	40.48	48	4675	11649	90612075
Hepatitis C	123.08	40.48	33	4690	5627	90618097
Hepatocellular carcinoma	118.01	40.48	27	4696	2401	90621323
Pruritus	96.36	40.48	129	4594	541396	90082328
Pyrexia	94.90	40.48	142	4581	660343	89963381
Photosensitivity reaction	93.10	40.48	35	4688	17772	90605952
Off label use	71.06	40.48	168	4555	1102084	89521640
Hepatic failure	52.36	40.48	30	4693	39698	90584026
Remission not achieved	50.65	40.48	9	4714	220	90623504
Jaundice	49.51	40.48	27	4696	32490	90591234
Hepatic function abnormal	48.11	40.48	30	4693	46258	90577466
Hepatic encephalopathy	44	40.48	19	4704	13753	90609971
Sunburn	43.55	40.48	13	4710	3254	90620470
Decreased appetite	42.83	40.48	73	4650	376467	90247257

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	563.01	29.23	299	5304	138282	42477450
White blood cell count decreased	407.49	29.23	224	5379	110172	42505560
Blood bilirubin increased	371.90	29.23	156	5447	42096	42573636
Anaemia	321.83	29.23	276	5327	280002	42335730
Hepatitis C	316.79	29.23	96	5507	10037	42605695
Hepatocellular carcinoma	274.92	29.23	82	5521	8112	42607620
Hyperbilirubinaemia	173.82	29.23	74	5529	20561	42595171
Haemoglobin decreased	162.21	29.23	136	5467	132335	42483397
Neutrophil count decreased	142.73	29.23	94	5509	63321	42552411
Photosensitivity reaction	142.64	29.23	56	5547	12646	42603086
Off label use	136.24	29.23	273	5330	638062	41977670
Jaundice	81.92	29.23	53	5550	34536	42581196
Remission not achieved	70.34	29.23	13	5590	150	42615582
Drug ineffective	69.65	29.23	210	5393	629987	41985745
Haemolytic anaemia	62.67	29.23	31	5572	12096	42603636
Pruritus	60.52	29.23	97	5506	188674	42427058
Sunburn	53.23	29.23	17	5586	2098	42613634
Hepatic failure	52.44	29.23	42	5561	38058	42577674
Genotype drug resistance test positive	48.93	29.23	14	5589	1190	42614542
Pyrexia	48.70	29.23	137	5466	393905	42221827
Hepatitis C RNA increased	45.21	29.23	10	5593	296	42615436
Treatment failure	45.00	29.23	48	5555	62576	42553156
Viral load increased	43.68	29.23	16	5587	2981	42612751
Hepatic encephalopathy	43.39	29.23	27	5576	16415	42599317
Ascites	41.71	29.23	44	5559	56634	42559098
Bilirubin conjugated increased	40.50	29.23	16	5587	3661	42612071
Thought blocking	39.97	29.23	8	5595	144	42615588
Choroiditis	34.39	29.23	11	5592	1364	42614368
Hyperuricaemia	34.14	29.23	19	5584	9405	42606327
Rash	33.81	29.23	96	5507	276858	42338874

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	1473.00	31.70	599	9034	229844	110349822
White blood cell count decreased	962.33	31.70	444	9189	228946	110350720
Anaemia	944.97	31.70	585	9048	546501	110033165
Blood bilirubin increased	749.08	31.70	272	9361	75700	110503966
Hepatitis C	440.72	31.70	119	9514	12454	110567212
Neutrophil count decreased	431.03	31.70	210	9423	120731	110458935
Haemoglobin decreased	428.40	31.70	267	9366	248460	110331206
Hepatocellular carcinoma	400.85	31.70	105	9528	9775	110569891
Hyperbilirubinaemia	332.35	31.70	118	9515	30553	110549113
Haemolytic anaemia	220.91	31.70	79	9554	20841	110558825
Photosensitivity reaction	149.94	31.70	63	9570	25526	110554140
Pyrexia	148.39	31.70	273	9360	897992	109681674
Pruritus	142.06	31.70	211	9422	581349	109998317
Jaundice	128.48	31.70	74	9559	59162	110520504
Remission not achieved	107.71	31.70	21	9612	506	110579160
Hepatic failure	100.99	31.70	67	9566	68672	110510994
Hepatic encephalopathy	74.06	31.70	40	9593	28216	110551450
Hepatitis C RNA increased	68.69	31.70	14	9619	425	110579241
Bilirubin conjugated increased	67.54	31.70	24	9609	6200	110573466
Ascites	62.54	31.70	57	9576	92751	110486915
Hyperuricaemia	60.01	31.70	28	9605	14503	110565163
Sunburn	58.85	31.70	20	9613	4528	110575138
Rash	57.36	31.70	179	9454	820785	109758881
Aspartate aminotransferase increased	57.10	31.70	70	9563	159866	110419800
Pain	56.75	31.70	8	9625	954947	109624719
Decreased appetite	53.69	31.70	124	9509	475722	110103944
Off label use	53.27	31.70	264	9369	1499921	109079745
Hepatorenal syndrome	50.92	31.70	18	9615	4579	110575087
Red blood cell count decreased	49.39	31.70	43	9590	65880	110513786
Hepatic function abnormal	49.05	31.70	49	9584	89246	110490420
Malaise	48.26	31.70	148	9485	671671	109907995
Insomnia	44.01	31.70	97	9536	360493	110219173
Alanine aminotransferase increased	43.63	31.70	66	9567	183707	110395959
Viral load increased	40.33	31.70	14	9619	3376	110576290
Thought blocking	38.69	31.70	8	9625	261	110579405
Choroiditis	37.10	31.70	11	9622	1604	110578062
Injection site pruritus	33.57	31.70	31	9602	51227	110528439
Injection site dermatitis	32.62	31.70	5	9628	26	110579640

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AP05	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011480	Protease Inhibitors
FDA MoA	N0000182138	Cytochrome P450 1A2 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000182638	HCV NS3/4A Protease Inhibitors
FDA EPC	N0000182639	Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA MoA	N0000193845	Bile Salt Export Pump Inhibitors
FDA MoA	N0000193960	Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA	N0000193965	Sodium Taurocholate Co-transporting Polypeptide Inhibitors
CHEBI has role	CHEBI:22587	antiviral agent

Related Drugs by ATC class:

J05AP Antivirals for treatment of HCV infections 18 drugs

asunaprevir beclabuvir boceprevir daclatasvir dasabuvir elbasvir glecaprevir grazoprevir ledipasvir ombitasvir paritaprevir pibrentasvir show all 18 →

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.35	acidic
pKa2	6.66	Basic
pKa3	3.5	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8349869	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8741926	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8754106	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9040562	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9353103	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9623022	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9856265	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8148399	Sept. 5, 2029	METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cathepsin S	Enzyme	P25774	CATS_HUMAN		IC50	6.10	CHEMBL
Hepatitis C virus serine protease, NS3/NS4A	Enzyme		A3EZI9_9HEPC D2K2A8_9HEPC	INHIBITOR	Ki	9.30	CHEMBL	CHEMBL
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	Ki	9.44	SCIENTIFIC LITERATURE	DRUG LABEL
Polyprotein	Polyprotein		Q6GYR8_9HEPC	INHIBITOR	Ki	9.44	IUPHAR
NS3 protease	Enzyme		C1KIQ2_9HEPC		Ki	9.40	CHEMBL
Genome polyprotein	Polyprotein		A3EZJ3_9HEPC		Ki	9.30	CHEMBL
Replicase polyprotein 1ab	Enzyme		R1AB_SARS2		IC50	8.61	CHEMBL
Nonstructural protein NS3-4A	Enzyme		A0A0K1CY61_9HEPC		Ki	9.44	CHEMBL

External reference:

ID	Source
D10081	KEGG_DRUG
4032900	VANDF
30B	PDB_CHEM_ID
CHEMBL501849	ChEMBL_ID
CHEMBL3137358	ChEMBL_ID
7367	IUPHAR_LIGAND_ID
1241946-89-3	SECONDARY_CAS_RN
DB06290	DRUGBANK_ID
9WS5RD66HZ	UNII
1482790	RXNORM
207569	MMSL
29896	MMSL
d08182	MMSL
015309	NDDF
015310	NDDF
708823009	SNOMEDCT_US
714167009	SNOMEDCT_US
C2605855	UMLSCUI
D000069616	MESH_DESCRIPTOR_UI
CHEBI:134743	CHEBI
9432	INN_ID
24873435	PUBCHEM_CID

Pharmaceutical products:

None

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simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Description:

Drug dosage:

ADMET properties:

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Approvals:

FDA Adverse Event Reporting System (Female)

FDA Adverse Event Reporting System (Male)

FDA Adverse Event Reporting System (Geriatric)

FDA Adverse Event Reporting System (Pediatric)

Pharmacologic Action:

Related Drugs by ATC class:

Drug Use | Suggest Off label Use Form| |View source of the data|

🐶 Veterinary Drug Use

🐶 Veterinary products

Acid dissociation constants calculated using MoKa v3.0.0

Orange Book patent data (new drug applications)

Orange Book exclusivity data (new drug applications)

Bioactivity Summary:

External reference:

Pharmaceutical products: